Regulatory Open Forum

Β View Only
  • 1.  MDR Significant Change, MDCG 2020-3 Chart E

    This message was posted by a user wishing to remain anonymous
    Posted 17-Jun-2021 08:32
    This message was posted by a user wishing to remain anonymous

    Hello Reg Experts!

    I have a question on whether a packaging change is considered a significant change under MDR Article 120.

    We have a Class I sterile device, with an MDD EC Certificate for "those aspects of Annex II relating to securing and maintaining sterility..."

    We are now considering changing from a sealed Tyvek/mylar pouch to a PETG tray with sealed Tyvek lid, using the same sterilization method (gamma) and contract sterilizer. Reviewing MDCG 2020-3 question E3, "Change in packaging design which affects functionality, safety, stability or seal integrity" seems to apply.

    We would complete packaging validation, transit testing, sterilization validation and shelf life testing on the new packaging design according to the same QMS procedures and the same applicable standards. So does this "affect" the functionality, safety, stability or seal integrity? If so, is the repeat testing per the same procedures and standards a reasonable rationale to conclude that it is not a significant change in the design or intended purpose per the regulation?

    I've been following the discussions here on NB's and guidance versus requirements. I'm very interested in your feedback on this particular situation.

    Would you approach your NB with the rationale and request written confirmation that the MDD certificate remains valid?


  • 2.  RE: MDR Significant Change, MDCG 2020-3 Chart E

    Posted 18-Jun-2021 02:40
    Good day Anon,

    In general, a change in packaging for a sterile product even in a normal circumstance would be considered a significant change.  A change in packaging would result in the need for the packaging validation, sterilisation validation, etc., as you mentioned in your post.  While I would agree with you in practicality using the same procedures, same contract steriliser, same methods, and standards may not represent a significant change, any change in packaging it typically considered a significant change.  Now, under the EU MDR Article 120 for EU MDD CE Certificates most Notified Bodies are taking the approach: any change requires upgrade to EU MDR.  I know your thinking, there is the guidance document and we can justify not being a significant change, but Notified Bodies are being conservative because of a number of reasons like they want companies moved to the EU MDR and more the legal basis for reviewing MDD CE Certificates gets very difficult for them.  To answer your question, you probably have a 0.01% chance of convincing your NB this is not a significant change and you can write a 30 page rationale for the MDD CE Certificate to remain valid, but it will probably end up in the same conclusion needing to update to EU MDR.  In honesty, you should devote your time, effort, resources, costs updating to EU MDR rather than spending the energy on justification for this change in packaging.

    ------------------------------
    Richard Vincins RAC
    Vice President Global Regulatory Affairs
    ------------------------------



  • 3.  RE: MDR Significant Change, MDCG 2020-3 Chart E

    Posted 18-Jun-2021 06:53
    Edited by Katarzyna Chrusciel 18-Jun-2021 21:49

    Good morning Anon,

    In your case, when the new material is used, I see mainly two problems that not allow to declare functional equivalence:

    1. Safety: microbial barrier and biocompatibility and toxicological attributes needs to be checked and confirmed
    2. Sealing: new material will require new OQ e PQ.


    The need for revalidation or verification of the sterilization process needs to be evaluated separately. Key aspects to consider are significant changes of porosity, potential impact on radiation penetration.

    The very well designed comparison table will be essential.

    A change of material is to be considered as a change of the design of the package and would normally require performance testing to be redone. The extend of the change can vary significantly.

    Transitioning to the same material from a new or different manufacturing line (or manufacturer) with identical specifications can hide risks, so that further analysis is required. Reviewing differences in the manufacturing process can be one option; however, this is usually not possible or only to a limited extent. If data is available indicating that the new material is performing in a similar way through the various processes of forming, sealing, sterilization, and generating packages fully within specifications, or in other words functionally equivalent, it could be the basis for a rationale to support the decision that previously documented performance testing data is sufficient to fulfil the requirement.

    When introducing the "same" material from a different converter, like reels or lids for a packaging machine, while the original material manufacturer and/or product are not changing, the extent of the change is normally only related to the material converting process steps, and risks to be examined would only include those related to these steps. Examples of aspects to consider would be the precision of the required dimensions, cleanliness, reel-winding tension, or printing aspects if applicable.

    Introducing a different type of film, different substrate, or different adhesive clearly requires a new design and process validation.

    Below, I will try to give you some additional information.

    The article 123.3 is the exemption to everything applying as of 26 May 2021 for legacy devices, but you still need to provide there are no significant changes in the design and intended purpose of the devices.

    Relevant parts of the Regulation MDR and EN ISO 13485:2016 gives us indication how to treat cases like yours.

    Art.10 p.9 states: Changes in device design or characteristics and changes in the harmonized standards or CS by reference to which the conformity of a device is declared shall be adequately taken into account in a timely manner.

    9a) a strategy for regulatory compliance, including compliance with conformity assessment procedures and procedures for management of modifications to the devices covered by the system;

    In addition Annex IX, 2.4 state: The manufacturer in question shall inform the notified body which approved the quality management system of any plan for substantial changes to the quality management system, or the device-range covered.

    If as manufacturer you decided to treat article 120.3 as a self-contained regime within the MDR, in which the old provisions of the Directives continue to apply, plus only the MDR elements explicitly mentioned in article 120.3 (you need to be able to run parallel QMS for legacy products), in any case you need to fulfill EN ISO 13485 (4.1.4, 7.2.3) requires that organization needs to communicate with regulatory authorities, including Notified Bodies, in accordance with regulatory requirements.

    Despite the fact that the wordings are slightly differing (substantial changes, significant changes) the authorities assume that in all cases only those changes need to be notified which "could affect conformity with the essential requirements". If this is the case, there is also a need for a further approval. Thus the criterion on when a change notification has to take place is identical to the criterion on whether a further approval is needed. The criterion for approving the change of the device is evidently the fulfilment of Essential Requirements applicable to the respective device and whether corresponding documentation has been updated correctly.

    Said this, I recommend you to contact and discuss with your Notified Body about any questions related to the substantial or not substantial characteristic of the change in order to get a common understanding.


    Best regards,

    K

    ------------------------------
    Katarzyna Chrusciel
    Engineer
    Italy
    ------------------------------



  • 4.  RE: MDR Significant Change, MDCG 2020-3 Chart E

    Posted 18-Jun-2021 14:38
    Edited by Katarzyna Chrusciel 18-Jun-2021 14:41
    In addition, to reply to your request β€œI've been following the discussions on NB's and guidance versus requirements. I'm very interested in your feedback on this particular situation.”

    I have my own opinion on this topic which  is not necessary  shared by other experts in this forum πŸ˜‰.

    Guidance documents are meant to provide assistance on how to comply with EU Regulations. They also serve to provide assistance to Manufacturers and NBs on how requirements should be implemented in a manner that is fair, consistent and effective.

    Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this documents may be acceptable provided they are supported by adequate justification. Alternate approaches should be discussed in advance with the NBs to avoid the possible finding that applicable regulatory requirements have not been met.

    K

    ---------------------------------
    Katarzyna Chrusciel
    Chemical, Clinical and Materials Engineer

    Italy
    ---------------------------------